[1,2]-Wittig Rearrangement

The [1,2]-Wittig Rearrangement is the base-promoted reaction of ethers to yield secondary or tertiary alcohols.

Mechanism of the [1,2]-Wittig Rearrangement

Compared to the [2,3]-Wittig Rearrangement,
the [1,2]-rearrangement has received little attention because of the somewhat
limited substrate scope and moderate yields. The mechanism has been fully
elucidated, and a discussion can be found in a recent publication by Nakai (J. Am. Chem. Soc., 1996,
118, 3317-3318. Abstract).

The [1,2]-Wittig Rearrangement is a carbanion rearrangement that proceeds via
a radical dissociation-recombination mechanism. The lithiated intermediate forms
a ketyl radical and a carbon radical, which give an alcoholate after fast
recombination within the solvent cage:

Despite its radical character, the integrity of the two radical stereocenters
is retained to an appreciable extent, with retention of configuration at the
migrating carbon and inversion at the lithium-bearing center:

Regioselectivity and ease of reaction are determined by the substituents. The
R-groups must be able to stabilize either an anion for the lithiation step, or a
radical to facilitate the migration step. For example benzyl groups are able to
stabilize both the anionic charge and the radical. Tertiary alkyl groups are
able to stabilize radicals, and the combination with a benzyl group thus gives
an ideal substrate:

Some other very suitable substrates have been reported; for example, O-glycosides
can be selectively converted in high yields to the C-glycosides:

For allyl-substituted substrates, the [2,3]-rearrangement
competes with [1,2]-rearrangement. Normally in these cases, the
[1,2]-rearrangement is only a source of side products. Keeping the temperature
as low as possible avoids contamination with these [1,2]-rearrangement products:

The regioselectivity can be better controlled if α-alkoxystannanes are used
as substrates. This modification is named the "Wittig-Still Rearrangement". Here,
the intermediate organolithium compound is produced through transmetallation:

The Wittig-Still Rearrangement is also a suitable starting point for
performing mechanistic studies about the stereospecificity of this process, and
Maleczka and Feng have reported on the stereochemical outcome of the
[1,2]-Wittig Rearrangement (J. Am. Chem. Soc., 1996,
118, 3317-3318.
DOI):

They found that the "normal" stereochemical tendency can be overcome by
specific intramolecular chelation effects:

Similar reactions can be performed using the less toxic α-alkoxysilanes as
starting materials: